Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103) / Cambios en la densidad mineral ósea y en el crecimiento en pacientes con acidosis tubular renal distal tras dos años de tratamiento con un nuevo fármaco alcalinizante (ADV7103)

Background and objectives: ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methods: Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. Results: After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. Conclusions: Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters. (AU)

Antecedentes y objetivo: El ADV7103 es un nuevo tratamiento de liberación prolongada para la acidosis tubular renal distal (ATRd), que contiene citrato potásico y bicarbonato potásico. Dado que la acidosis puede afectar al contenido mineral óseo, se ha evaluado el efecto de dicho medicamento a lo largo de 24 meses sobre la densidad mineral ósea (DMO) y el crecimiento en pacientes con ATRd. Pacientes y métodos: Se incluyeron treinta pacientes (24 pediátricos y seis adultos) en un estudio abierto de extensión tras un ensayo clínico de fase II/III. La DMO medida por densitometría se midió al inicio del estudio y los 24 meses. El crecimiento se evaluó a lo largo del estudio. Adicionalmente, se determinaron el bicarbonato plasmático, la parathormona, 25 hidroxivitamina D, 1,25 dihidroxivitamina D, fosfatasa alcalina ósea, calciuria y citraturia. La seguridad y el cumplimento terapéutico también fueron evaluados. Resultados: Tras 24 meses de tratamiento con ADV7103 la media del z-score de DMO de columna aumentó significativamente frente al valor basal (p = 0,024). En los adultos el z-score de la densitometría de columna y corporal total mostró una correlación significativa con los valores de bicarbonato plasmático (rS = 0,82 y rS = 0,97, respectivamente, p < 0,005). Se registró un incremento > 0,5 unidades de z-score para altura y peso en el 18 y 36%, respectivamente, de los pacientes pediátricos. Con el tratamiento, la concentración plasmática de bicarbonato y la calciuria fueron normales en las diferentes visitas en un 69-86% y un 93-96% de los pacientes, respectivamente. Solamente se notificaron nueve eventos adversos gastrointestinales relacionados con el tratamiento, todos de intensidad leve/moderada en cinco pacientes. Conclusiones: Dos años de tratamiento con ADV7103 mejoraron el crecimiento y la DMO de columna. Estos resultados sugieren que el control de la acidosis con dicho tratamiento provoca una mejora de parámetros óseos. (AU)

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103).

BACKGROUND AND OBJECTIVES: ADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. PATIENTS AND METHODS: Thirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. RESULTS: After 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69-86% and 93-96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. CONCLUSIONS: Two years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis.

BACKGROUND: A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months. METHODS: Thirty pediatric and adult patients were included in an open-label extension study after a phase II/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored. RESULTS: There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69-86% and 83-93% of patients. Overall adherence rates were ≥ 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study. CONCLUSIONS: Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable. TRIAL REGISTRATION NUMBER: Registered as EudraCT 2013-003828-36 on the 3rd of September 2013.

Acidosis tubular renal distal (ATRd): aspectos epidemiológicos, diagnósticos, de seguimiento clínico y terapéuticos. Resultados de una encuesta a un colectivo de nefrólogos / Distar Renal Tubular Acidosis (dRTA): Epidemiological, diagnostics, clinical follow-up and therapeutical issues. Nephrologists cohort survey outcome

ANTECEDENTES Y OBJETIVOS: La acidosis tubular renal distal (ATRd) es una enfermedad minoritaria, de origen genético o adquirido, caracterizada por una incapacidad de excreción urinaria de hidrogeniones (H+), hipobicarbonatemia, hipercloremia, hipocitraturia y habitualmente hipokaliemia e hipercalciuria. Las formas genéticas suelen diagnosticarse en los primeros meses de vida y su tratamiento consiste en suplementos de álcali encaminados a evitar las consecuencias clínicas a largo plazo, sobre todo la enfermedad renal crónica (presente en algunas series hasta en el 82% de los pacientes) y la enfermedad ósea asociada. Se desarrolló una encuesta multirrespuesta cerrada de 10 preguntas encaminada a conocer aspectos epidemiológicos, diagnósticos, del manejo clínico y terapéutico, dentro del colectivo de nefrólogos españoles. MATERIALES Y MÉTODOS: Encuesta distribuida a los asistentes a un foro científico sobre ATRd durante el congreso de 2019 de la Sociedad Española de Nefrología (SEN); las respuestas se recogieron a la salida del mismo. Los resultados se analizaron con un test estadístico paramétrico estableciéndose el porcentaje de cada respuesta a las 10 preguntas. RESULTADOS: De entre los que respondieron a la encuesta, el 44,4 y el 37,7% no atendieron a ningún paciente con ATRd en el último año ni en los tres anteriores, respectivamente. Cuando se sospecha la patología, el diagnóstico genético confirmatorio se realiza solo en el 13,3% de los casos y el estudio familiar solo en el 11,1%. Solo el 26,6% afirman que el control metabólico es excelente, bueno o muy bueno, y el 69% piensan que el cumplimiento terapéutico es regular, malo o muy malo. CONCLUSIONES: La encuesta ha puesto de manifiesto el relativo desconocimiento de esta patología, así como la baja satisfacción con el control metabólico y el pobre cumplimiento terapéutico, lo cual puede conllevar una mayor severidad en la enfermedad renal y ósea asociadas a la ATRd

BACKGROUND AND OBJECTIVES: dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists. MATERIALS AND METHODS: This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. RESULTS: Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good, and 69% of the responders believe that treatment compliance is not bad, bad or very bad. CONCLUSIONS: This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA

Distar Renal Tubular Acidosis (dRTA): Epidemiological, diagnostics, clinical follow-up and therapeutical issues. Nephrologists cohort survey outcome.

BACKGROUND AND OBJECTIVES: dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists. METHODS AND MATERIALS: This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. RESULTS: Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good. 69% of the responders believe that treatment compliance is not bad, bad or very bad. CONCLUSIONS: This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA.

Distar Renal Tubular Acidosis (dRTA): Epidemiological, diagnostics, clinical follow-up and therapeutical issues. Nephrologists cohort survey outcome. / Acidosis tubular renal distal (ATRd): aspectos epidemiológicos, diagnósticos, de seguimiento clínico y terapéuticos. Resultados de una encuesta a un colectivo de nefrólogos.

BACKGROUND AND OBJECTIVES: dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists. MATERIALS AND METHODS: This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. RESULTS: Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good, and 69% of the responders believe that treatment compliance is not bad, bad or very bad. CONCLUSIONS: This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA.